CONTRASTING RESPONSE OF LUNG PARENCHYMAL-CELLS TO INSTILLED TNF-ALPHAAND IFN-GAMMA - THE INDUCIBILITY OF SPECIFIC CELL ICAM-1 IN-VIVO

Induction of intercellular adhesion molecule-1 (ICAM-1) by proinflamma tory cytokines during inflammation plays an important role in regulati ng polymorphonuclear neutrophil (PMN) migration and localization. In t his report, we examined the effects of tumor necrosis factor-alpha (TN F alpha) and interferon-gamma (IFN gamma) on specific lung cell expres sion of ICAM-1 in who and the accompanying morphological changes. Balb -c mice were treated with phosphate-buffered saline (PBS) alone or wit h PBS containing 5 mu g TNF alpha or IFN gamma through intranasal inst illation. Twenty-four hours after treatment, their lungs were processe d for immunoblot analysis and electron microscope immunocytochemistry. In the normal lung, the ICAM-1 level is high on type I alveolar epith elial cells, medium on arterial and venous endothelial cells, low on t ype II epithelial cells and capillary endothelium, and not detectable on bronchial epithelium. Topical treatment of the lung with either TNF alpha or IFN gamma induced a 50-60% increase in total lung and alveol ar ICAM-1.IA dramatic increase of alveolar type II cell surface ICAM-1 was observed (> 20-fold). Both cytokines caused 2-3-fold higher ICAM- 1 expression on capillary endothelial cells and a 40% increase of ICAM -1 on alveolar type I cells that was not uniform. However, due to the large total surface area of type I epithelium, type I cells contribute 70-86% of total alveolar septal ICAM-1 and > 90% of alveolar surface ICAM-1 in either treated or normal mouse lungs. Increased ICAM-1 expre ssion was also observed on nonparenchymal endothelial and epithelial c ells, Margination and sequestration of PMN in cytokine-treated lungs w ere observed by histologic examination, measurements of total lung myl operoxidase activity, and number of neutrophils recovered in bronchoal veolar lavage fluid. These results showed that TNF alpha and IPN gamma induce ICAM-1 expression and infiltration of neutrophils in the lung. The response of specific lung cells in terms of induction of ICAM-1 i n response to cytokine stimulation varied significantly particula rly between type I and type IT epithelial cells.